The program proposed will continue to have four major research divisions. The first will be concerned with renal disease and transplantation emphasizing (a) mechanisms involved in experimental and clinical allograft rejection, (b) means of preventing rejection by enhancing procedures, and (c) methods of evaluating diagnostic and management techniques to detect and abrogate rejection. The second will concentrate on methods to examine by ultrastructural and chemical techniques, cellular membrane systems and their response to, and role in free radical, immunological and other forms of cellular injury as observed in man and producible in the experimental animal. The third will investigate the mechanisms of target cell destruction by cellular and humoral processes including the effects of lymphokines and other cell products as modulators of cell growth and proliferation. The fourth division will attempt analysis of tissue damaging processes by morphometric techniques to evaluate progression and possibly regression of diseases affecting the major viscera and correlating such measurements with clinical, functional, chemical and radiological parameters. These approaches would be applied particularly to acute myocardial and acute pulmonary injury.